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Exp Neurol. 2018 Apr;302:75-84. doi: 10.1016/j.expneurol.2017.12.013. Epub 2017 Dec 29.

Electrical stimulation as a conditioning strategy for promoting and accelerating peripheral nerve regeneration.

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Department of Surgery, University of Alberta, Alberta, Canada.
Department of Anatomy and Cell Biology & Cameco MS Neuroscience Research Center, University of Saskatchewan, Saskatchewan, Canada.
Division of Physical Medicine and Rehabilitation, University of Alberta, Alberta, Canada.
Department of Surgery, University of Alberta, Alberta, Canada. Electronic address:


The delivery of a nerve insult (a "conditioning lesion") prior to a subsequent test lesion increases the number of regenerating axons and accelerates the speed of regeneration from the test site. A major barrier to clinical translation is the lack of an ethically acceptable and clinically feasible method of conditioning that does not further damage the nerve. Conditioning electrical stimulation (CES), a non-injurious intervention, has previously been shown to improve neurite outgrowth in vitro. In this study, we examined whether CES upregulates regeneration-associated gene (RAG) expression and promotes nerve regeneration in vivo, similar to a traditional nerve crush conditioning lesion (CCL). Adult rats were divided into four cohorts based on conditioning treatment to the common peroneal (fibular) nerve: i) CES (1h, 20Hz); ii) CCL (10s crush); iii) sham CES (1h, 0Hz); or iv) naïve (unconditioned). Immunofluorescence and qRT-PCR revealed significant RAG upregulation in the dorsal root ganglia of both CES and CCL animals, evident at 3-14days post-conditioning. To mimic a clinical microsurgical nerve repair, all cohorts underwent a common peroneal nerve cut and coaptation one week following conditioning. Both CES and CCL animals increased the length of nerve regeneration (3.8-fold) as well as the total number of regenerating axons (2.2-fold), compared to the sham and naïve-conditioned animals (p<0.001). These data support CES as a non-injurious conditioning paradigm that is comparable to a traditional CCL and is therefore a novel means to potentially enhance peripheral nerve repair in the clinical setting.


Axon regeneration; Brain derived neurotrophic factor; Conditioning lesion; Electrical stimulation; Glial fibrillary acidic protein; Growth associated protein-43; Microsurgical repair; Nerve regeneration; Peripheral nerve; Regeneration-associated genes

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